Method for treatment of solid pharmaceutical preparation prior to printing and solid pharmaceutical preparation subjected to treatment prior to printing

ABSTRACT

The present invention provides a method for treating a solid dosage form to improve the printability and abrasion resistance of a print to be produced on a surface of the solid dosage form, which includes treating the surface of the solid dosage form with a polyethylene glycol-containing aqueous solution before printing; a production method of a solid dosage form with a printed surface, which includes printing on the surface after the aforementioned treatment; and a solid dosage form having a print improved in abrasion resistance on its surface, which can be obtained by the aforementioned production method.

TECHNICAL FIELD

The present invention relates to a method for treating a solid dosageform to improve the printability and abrasion resistance of a print tobe produced on a surface of the solid dosage form, and a solid dosageform having improved abrasion resistance of a print or improvedprintability, which is afforded by the treatment.

BACKGROUND ART

There are many kinds of tablets and capsules that resemble one anotherin the size, color tone and shape. To identify each preparation, acompany name, a company mark, a product name, ingredient contents andthe like are often coded and directly imprinted on the preparation. Forimprinting, engraving and printing are available. While engraving isemployed for plain tablets free of coating, a subset of film-coatedtablets and the like, printing is employed for many film-coated tablets,sugar-coated tablets, capsules and the like.

For tablets and capsules, polishing with wax (in this specification, itmeans “wax” in a narrow sense, namely, fatty acid ester of higheralcohol; examples: carnauba wax, bees wax and the like) is often appliedfor the purpose of increasing the commercial value by glossy appearance,protecting a preparation from highly humid environment, preventingstaining with coloring agents, improving slip property to facilitatehandling in later operations of printing, inspection, packing and thelike, and the like (e.g., Porter and two others, Pan Coating of Tabletsand Granules, edited by Herbert A. Lieberman and one other,Pharmaceutical Dosage Forms Tablets, vol. 3, US, Marcel Dekker Inc.,1982, p. 92). Wax can be used by dissolving in an organic solvent suchas chloroform/acetone and the like, or suspending in a dispersion mediumsuch as alcohol and the like, or directly applied to the surface of apreparation as a fine powder. However, it is desirable to avoid use ofan organic solvent in view of the safety issue caused by a residualsolvent, a large scale facility required to prevent accident andenvironmental pollution, and the like. Moreover, the use of a suspensionand a powder may cause non-uniform coating, possibly leading toinconvenience.

Furthermore, polishing with a wax prior to printing may cause easyscratch of prints and stain of the preparation itself as well ascontainers, which in turn impairs identification function and alsoreduces the commercial value due to the defective appearance. Inaddition, some kind of wax provides too much polish that can causeprinting failure, and decrease the product yield (e.g., U.S. Pat. No.4,456,629 (column 1, lines 34-39)).

DISCLOSURE OF THE INVENTION

It is therefore an object of the present invention to provide a methodof polishing a solid dosage form without using an organic solvent, whichcan improve and abrasion resistance of a print and printability of thesolid dosage form, and a solid dosage form improved in the abrasionresistance of a print and/or printability based on the method.

The present inventors have conducted intensive studies in an attempt tosolve the aforementioned problem and surprisingly found that theprintability during printing and abrasion resistance of the print afterprinting of a solid dosage form can be remarkably improved, as comparedto conventional tablets polished with a wax, by treating a surfacethereof with a polyethylene glycol-containing aqueous solution prior toprinting. The present inventors have conducted further studies based onthese findings and completed the present invention.

Accordingly, the present invention provides

-   [1] a treatment method for improving printability and/or abrasion    resistance of a print to be produced on a surface of a solid dosage    form, which comprises treating said surface with a polyethylene    glycol-containing aqueous solution before printing,-   [2] the method of the above-mentioned [1], wherein polyethylene    glycol has an average molecular weight of not less than about 1,000,-   [3] the method of the above-mentioned [1], wherein polyethylene    glycol has an average molecular weight of about 3,000 to about    9,000,-   [4] the method of the above-mentioned [1], wherein the amount of    polyethylene glycol to be added by the treatment is about 0.01% to    about 1.0% in a weight ratio to the finished preparation,-   [5] the method of the above-mentioned [1], wherein the solid dosage    form is a film-coated tablet,-   [6] a method for producing a solid dosage form with a printed    surface, which comprises treating the surface of the solid dosage    form with a polyethylene glycol-containing aqueous solution and then    printing on said surface,-   [7] the method of the above-mentioned [6], wherein polyethylene    glycol has an average molecular weight of not less than about 1,000,-   [8] the method of the above-mentioned [6], wherein polyethylene    glycol has an average molecular weight of about 3,000 to about    9,000,-   [9] the method of the above-mentioned [6], wherein the amount of    polyethylene glycol to be added by the treatment is about 0.01% to    about 1.0% in a weight ratio to the finished preparation,-   [10] the method of the above-mentioned [6], wherein the solid dosage    form is a film-coated tablet,-   [11] a solid dosage form treated by the method of any of the    above-mentioned [1] to [5],-   [12] a solid dosage form with a printed surface, which can be    obtained by any of the above-mentioned [6] to [10],-   [13] a solid dosage form which has a coating film comprising    polyethylene glycol but free of bees wax and carnauba wax on its    surface, and is printed on the surface of the coating film, and-   [14] a solid dosage form which has a coating comprising polyethylene    glycol but free of bees wax and carnauba wax on its surface, and is    printed on the surface of the coating.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a method for treating a solid dosage formto improve the abrasion resistance of a print to be produced on asurface of the solid dosage form. As used herein, by “to improve theabrasion resistance of a print” is meant, for example, significantlyreducing the degree of abrasion of the print produced on the soliddosage form as compared to a case free of such treatment, in the printabrasion test to be described in detail in the Examples to be mentionedbelow.

The solid dosage form applicable to the treatment method of the presentinvention is not particularly limited in the dosage form as long as itssurface can be printed on and, for example, tablet, capsule, troche,pill, suppository and the like can be mentioned. In view of thenecessity of imprinting by printing, the method is particularlypreferably applied to tablets and capsules.

In this specification, the “solid dosage form” means not onlypharmaceutical products but also any composition processed to have acertain dosage form of animal drug, agricultural chemical, fertilizer,sanitary products and the like.

The active ingredient to be contained in the solid dosage form is notparticularly limited. For example, substances effective for theprophylaxis or treatment of various diseases, which are exemplified by,but not limited to, substances having sleep-inducing action,tranquilizer activity, antibiotic activity, hypotensive action,antianginal activity, analgesic activity, anti-inflammatory activity,mental stabilizing action, diabetes treatment activity, diuretic action,anticholine activity, antihyperacidic action, antiepileptic action, ACEinhibitory activity, β-receptor antagonistic or agonistic activity,anesthetic action, anorexigenic action, antiarrhythmic action,antidepressive action, anticoagulant activity, anti diarrheal action,antihistaminic activity, antimalarial action, antitumor activity,immunosuppressive activity, anti-Parkinson's syndrome action,antipsychotic action, antiplatelet activity, antihyperlipidemic actionand the like, and the like, substance having detergent action,substances having flavoring, fertilizer, and deodorizing actions,animal/pest exterminating substances, substances having insecticidalaction, substances having herbicidal action, plant growth regulators andthe like.

Where necessary, the solid dosage form of the present invention cancontain a carrier acceptable for the use of the solid dosage form,together with the active ingredient. In the case of a pharmaceuticalpreparation, for example, it can contain a pharmaceutically acceptablecarrier. As the pharmaceutically acceptable carrier, various organic orinorganic carriers conventionally used as preparation materials are usedand, for example, excipient, lubricant, binder, disintegrant, thickenerand the like are appropriately added in suitable amounts. Wherenecessary, additives such as preservative, antioxidant, coloring agent,sweetening agent and the like can also be used.

Examples of the excipient include, but are not limited to, lactose,sucrose, glucose, maltose, corn starch, flour starch, mannitol, xylitol,sorbitol, maltitol, erythritol, lactitol, palatinit, crystallinecellulose, light anhydrous silicic acid, dextrin, carboxymethylstarch,gelatin, synthesis aluminum silicate, magnesium alumino metesilicate,magnesium oxide, calcium phosphate, calcium carbonate, calcium sulfateand the like.

Examples of the lubricant include, but are not limited to, stearic acid,magnesium stearate, calcium stearate, talc, waxes, DL-leucine, sodiumlauryl sulfate, magnesium lauryl sulfate, polyethylene glycol, aerosil(usable as antistatic agent) and the like.

Examples of the binder include, but are not limited to, gelatin,pullulan, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose(HPC), methylcellulose (MC), crystalline cellulose, polyvinylpyrrolidone(PVP), polyethylene glycol, gum arabic, dextran, polyvinyl alcohol(PVA), starch paste and the like.

Examples of the disintegrant include, but are not limited to,carboxymethylcellulose, calcium carboxymethylcellulose, low-substitutedhydroxypropylcellulose, crosslinking polyvinylpyrrolidone, carmellosesodium, croscarmellose sodium, sodium carboxymethyl starch, cationexchange resin, partially pregelatinized starch, corn starch and thelike.

Examples of the thickener include, but are not limited to, naturalrubbers, cellulose derivative, acrylic acid polymer and the like.

Examples of the preservative include, but are not limited to,p-hydroxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethylalcohol, dehydroacetic acid, sorbic acid and the like.

Examples of the antioxidant include, but are not limited to, sulfite,ascorbic acid and their alkali metal salts, alkaline earth metal saltsand the like.

Examples of the coloring agent include, but are not limited to,synthetic coloring agents applicable to pharmaceutical products (e.g.,sunset yellow etc. and aluminum lake thereof and the like), yellowferric oxide, red ferric oxide, riboflavin, riboflavin organic acidesters (e.g., riboflavin butyric acid ester), phosphoric acid riboflavinor alkali metal salt thereof, alkaline earth metal salt, phenolphthalein, titanium oxide and the like. As the light shielding agent,titanium oxide and the like can be mentioned.

Examples of the sweetening agent include, but are not limited to,saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia and thelike.

The solid dosage form of the present invention can be formulated into adosage form suitable for oral administration, which is exemplified by,but not limited to, tablet, capsule and the like or parenteraladministration such as suppository and the like, by processing theabove-mentioned active ingredient and a suitable carrier according to amethod known per se.

Tablets can be coated by a method known per se for the purpose ofmasking a smell or taste, stabilizing components, maintaining efficacyand the like. The coating can be largely divided into sugar coating andfilm coating (including enteric coating and the like) according to itskind.

As a coating agent for sugar coating, sucrose is generally used. Toenhance the binding property of a sugar coating layer and increase themechanical strength, gelatin, gum arabic, methylcellulose,carboxymethylcellulose, sodium carboxymethylcellulose, sodiumstarchglycolate, crystalline cellulose, polyvinylpyrrolidone, polyvinylalcohol, sodium alginate and the like can be added. Furthermore, as anexcipient or anti-tack agent, talc, precipitated calcium carbonate,kaolin and the like are used, and, for masking or shading of color, amasking agent such as titanium oxide and the like are used.

As the film coating agent, for example, hydroxypropylmethylcellulose,ethylcellulose, hydroxypropylcellulose, tween80, and dyes such astitanium oxide, ferric oxide (e.g., red ferric oxide, yellow ferricoxide) and the like are used. Moreover, photostability and the like canbe improved by adding a masking agent and the like. These film coatingformulations may contain, where necessary, talc and other excipientsapplicable to pharmaceutical products. As the film coating agent, a baseagent aiming at enteric coating and controlled release may be usedbesides those used for masking a taste, enhancing photostability orimproving appearance. As a base agent for the film coating,hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC),polyvinylpyrrolidone (PVP), ethylcellulose, polyvinyl acetaldiethylamino acetate, cellulose acetate phthalate, methacrylic acidcopolymers (e.g., methyl methacrylate-methacryl acid copolymers(Eudragit L100 or S100, manufactured by Rohm), methacrylic acid-ethylacrylate copolymers (Eudragit L100-55, L30D-55), methacrylic acid-methylacrylate-methyl methacrylate copolymers (Eudragit FS30D, manufactured byRohm)), hydroxypropylmethylcellulose phthalate (HP-55, HP-50,manufactured by Shin-Etsu Chemical Co., Ltd.),carboxymethylethylcellulose (CMEC, manufactured by Freund Corporation),hydroxypropylcellulose acetate succinate (HPMCAS, manufactured byShin-Etsu Chemical Co., Ltd.), polyvinyl acetate phthalate, shellac andthe like can be used. They may be used alone, or at least two or morekinds of polymers may be applied in combination, or at least two or morekinds of polymers may be applied successively.

Of these, as a coating material for controlling the release of theactive ingredient in a pH-dependent manner, hydroxypropylmethylcellulosephthalates (HP-55, HP-50, manufactured by Shin-Etsu Chemical Co., Ltd.),cellulose acetate phthalate, carboxymethylethylcellulose (CMEC,manufactured by Freund Corporation), methyl methacrylate-methacrylicacid copolymers (Eudragit L100 or S100, manufactured by Rohm),methacrylic acid-ethyl acrylate copolymers (Eudragit L100-55, L30D-55),methacrylic acid-methyl acrylate-methyl methacrylate copolymer (EudragitFS30D, manufactured by Rohm), hydroxypropylcellulose acetate succinate(HPMCAS, manufactured by Shin-Etsu Chemical Co., Ltd.), polyvinylacetate phthalate, shellac and the like can be used.

The coating agents may be used alone or in combination as necessary.Where necessary, plasticizer, stabilizer and the like such aspolyethylene glycol, dibutyl sebacate, diethyl phthalate, triacetine,triethyl citrate, copolyvidon and the like may be used for coating.

For coating, a method known per se, such as a pan coating method using aperforated coating system (e.g., Hicoater (trademark); FreundCorporation) and the like using a coating pan, a fluid bed coatingmethod using a fluid bed granulation coating system (e.g., flow coater(trademark); Freund Corporation) and the like, is employed.

Capsules can be produced by packing the above-mentioned activeingredient powder, or a powder mixture of the active ingredient and theabove-mentioned carrier, or fine granules or granules obtained bykneading or granulating the powder mixture and the like in a suitablecapsule. The packed material (particularly fine particles or granules)may be film-coated as necessary, in a similar manner as that mentionedabove with regard to the tablet.

As the capsule, one containing polyhydric alcohol such as glycerol,propylene glycol and the like or saccharide such as mannitol, sorbit andthe like as a plasticizer in gelatin, which is molded suitably can bementioned. Where necessary, the capsule may further contain a coloringagent and a preservative similar to those mentioned above.

The treatment method of the present invention may be applied to acapsule filled with the packing material such as an active ingredientand the like. Alternatively, an empty capsule may be subjected to thetreatment method of the present invention, printed and filled with apacking material to give a finished preparation.

The treatment method of the present invention can also be applied notonly to the above-mentioned solid dosage form but also any solidcomposition desired to carry a print on its surface such as a food(e.g., sugar coated chocolate, gum, supplement and the like) and thelike, particularly a solid composition requiring or desirably subjectedto a treatment for improving the slip property and gloss.

The treatment method of the present invention is characterized by atreatment of a surface of the solid dosage form with a polyethyleneglycol-containing aqueous solution before printing. As used herein, bythe “treatment” is meant “to apply” and refers to bringing apolyethylene glycol-containing aqueous solution into contact with thesurface of a solid dosage form after treatment, such that polyethyleneglycol remains on the surface.

Polyethylene glycol to be used in the present invention is notparticularly limited as long as it is not subject to any limitation dueto other reasons (e.g., range acceptable as a pharmaceutical additivewhen the solid dosage form is a pharmaceutical preparation). Inconsideration of the object of the present invention to improvedurability of a print, however, polyethylene glycol is desirably presentas a solid at a temperature of the environment (e.g., 0 to 40° C., 10 to30° C., 15 to 25° C.) where the solid dosage form is preserved. Forexample, one having an average molecular weight of about not less than1,000, more preferably about 3,000 to about 9,000, can be mentioned. Inaddition, two or more kinds of polyethylene glycol having differentaverage molecular weights may be used in a mixture.

The average molecular weight of polyethylene glycol is measured by amethod according to the measurement method of the average molecularweight of macrogol 4000 in the Japan Pharmacopoeia fourteenth Edition(hereinafter sometimes to be abbreviated simply as the JapanPharmacopoeia).

The concentration of polyethylene glycol in the polyethyleneglycol-containing aqueous solution is not particularly limited as longas it ensures that polyethylene glycol remains on the surface of a soliddosage form after treatment in an amount sufficient to improve theabrasion resistance of a print to be produced on said surface. Forexample, it is about 1 to about 20 wt %, preferably about 5 to about 15wt %.

The polyethylene glycol-containing aqueous solution can contain acomponent other than polyethylene glycol within the range free of a badinfluence on the property of a print to be produced on the surface of asolid dosage form. As used herein, by the “property of a print” is meantproperties including quantitative and qualitative characteristics duringprinting, such as abrasion resistance after printing, incidence ofincomplete print, printing stain and the like (=rate of printingfailure) and level of the printing failure. For example, when thetreatment method of the present invention is applied to a plain tablet,the polyethylene glycol-containing aqueous solution contains a filmcoating agent since the solution also functions as a film coatingliquid, as mentioned above. As the film coating agent, for example,those capable of being dispersed in a water-soluble or aqueous solutioncan be mentioned, from the above-mentioned film coating agents.

In addition, the polyethylene glycol-containing aqueous solution canfurther contain a preparation additive as necessary, such as stabilizer,lubricant, preservative, antioxidant, coloring agent, sweetening agentand the like. As the stabilizer, for example, tartaric acid, citricacid, succinic acid, fumaric acid, maleic acid and the like can bementioned. As the lubricant, for example, talc, titanium oxide,magnesium stearate, calcium stearate, light anhydrous silicic acid andthe like can be mentioned. As the preservative, for example,p-hydroxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethylalcohol, dehydroacetic acid, sorbic acid and the like can be mentioned.As the antioxidant, for example, sulfite, ascorbate and the like can bementioned. As the coloring agent, for example, water-soluble food tarcolors (e.g., food dyes such as Food Red No. 2 and No. 3, Food YellowNo. 4 and No. 5, Food Blue No. 1 and No. 2 and the like), waterinsoluble lake colors (e.g., aluminum salts of the aforementionedwater-soluble food tar colors), natural colors (e.g., B-carotene,chlorophyll, ferric oxide) and the like can be mentioned. As thesweetening agent, for example, sodium saccharin, dipotassiumglycyrrhizinate, aspartame, stevia and the like can be mentioned.

As mentioned above, the film coating liquid can contain a plasticizer tocontrol the softening temperature of the coating agent. When thepolyethylene glycol-containing aqueous solution is a film coatingliquid, polyethylene glycol itself can function as a plasticizer. Apolyethylene glycol-containing aqueous solution having a concentrationnecessary for improving the abrasion resistance of a print to beproduced on the surface of a solid dosage form is sufficient to functionas a plasticizer. When desired, other plasticizers, such asacetyltributyl citrate, acetyltriethyl citrate, castor oil,diacetylation monoglyceride, dibutyl sebacate, diethyl phthalate,glycerol, mono- or di-acetylation monoglyceride, propyleneglycol,triacetine, triethyl citrate and the like may be further added.

When the polyethylene glycol-containing aqueous solution contains acomponent other than polyethylene glycol, the proportion of polyethyleneglycol in the whole components (excluding water) is about 1 to about 30wt %, preferably about 10 to about 20 wt %.

For a treatment of the surface of a solid dosage form with apolyethylene glycol-containing aqueous solution, various coating methodsgenerally used in the field of preparations can be employed. Preferably,spray coating is applied using a coating pan, a fluid bed coating systemand the like.

In the case of sugar-coated tablets, for example, after completion ofeach step of sugar coating (i.e., waterproof coating, under coating,sub-coating, coloring, finishing), tablets are transferred to a clothpolishing pan, a predetermined amount of a polyethyleneglycol-containing aqueous solution is sprayed or poured thereon whilerotating the pan, or a polyethylene glycol-containing aqueous solutionis sprayed or poured thereon once to several times while rotating thepan until it reaches a predetermined coating weight.

In the case of film-coated tablets, for example, a polyethyleneglycol-containing aqueous solution is sprayed with a compressed air froma spray nozzle in the coating pan used for the film coating whilerotating the pan, and the surface of the tablets is dried by heated airsupplied. Alternatively, in the fluid bed coating system used for thefilm coating, a polyethylene glycol-containing aqueous solution issprayed from a spray nozzle while floating or fluidizing the tabletswith an air flow and the surface of the tablets is dried with the airflow. The polyethylene glycol-containing aqueous solution is sprayed ina predetermined amount, or the above-mentioned operation is repeateduntil a predetermined coat weight is achieved.

In the case of plain tablets, namely, when a polyethyleneglycol-containing aqueous solution also functions as a film coatingliquid, a method employed for conventional film coating can be useddirectly. For example, a method similar to that of the above-mentionedfilm-coated tablets can be mentioned.

In the case of capsule, too, a method employed for conventional filmcoating can be used similarly. When this treatment is applied afterfilling packing materials such as an active ingredient and the like,powder of the packing materials attached to the surface of the capsuleduring the filling is preferably removed with a conventional capsulepolishing machine before the treatment.

The weight of the coating film formed by the treatment method of thepresent invention is not particularly limited as long as it ensures thatpolyethylene glycol remains on the surface of a solid dosage form aftertreatment in an amount sufficient to improve the abrasion resistance ofa print to be produced on said surface. Preferably, it is appropriatelyselected from the range that makes the weight ratio of the amount ofpolyethylene glycol to be added by this treatment to the finishedpreparation fall within the range of about 0.01 to about 1.0%, morepreferably about 0.05 to about 0.7%.

The treatment method of the present invention can not only improve theabrasion resistance of a print to be produced on the surface of a soliddosage form, but also reduce the frequency of printing failure (i.e.,printing failure rate) during printing such as incomplete print,printing stain and the like, and advantageously further improve theprinting performance as a whole.

Accordingly, the present invention also relates to a production methodof a solid dosage form having a print on its surface, which comprisestreating the surface of the solid dosage form with a polyethyleneglycol-containing aqueous solution and then printing on said surface.The treatment with a polyethylene glycol-containing aqueous solution canbe applied as mentioned above.

For printing, a method conventionally used in the art can be employed.As a solid dosage form delivery mechanism of a printing machine, anytype can be used, including a slot type, a drum type, a link type andthe like, and an appropriate type can be selected according to themanufacturing scale and the like. While the printing method is notparticularly limited, either, a photogravure offset printing method isoften used. To be specific, a photogravure roll engraved with anidentification code, a symbol and the like during a photomechanicalprocess is rotated in an ink tank to attach the ink, and redundant inkis scraped off with a blade (thin-bladed knife). The ink remaining inthe engraving (concave) is transferred onto a rubber offset roll, andthen transferred onto the solid dosage form in a printing section tocomplete the printing. As the tablet (capsule) printing machine,commercially available ones from Markem Corporation, Hartnett, MatsuokaMachinery Works Co., Ltd, Qualicaps Co., Ltd. and the like can be used.

While the ink to be used for printing is not particularly limited aslong as it is harmless, it is desirably quick-drying, and has highabrasion resistance after drying.

As the dye, titanium oxide, carbon black, iron oxide, tar dyes (e.g.,acidic colors such as Red No. 2, Red No. 3, Red No. 102, Red No.104-(1), Red No. 105-(1), Red No. 106, Yellow No. 4, Yellow No. 5, GreenNo. 5, Blue No. 1, Blue No. 2 and the like) and the like are generallyused. As the base agent, moreover, shellac and the like are used and, asthe solvent, ethanol, n-butanol, isopropanol and the like are used.

The solid dosage form with a print on its surface, which is produced bythe above-mentioned method, has novel and useful characteristic in thatit shows remarkably improved abrasion resistance of prints as comparedto conventional preparations obtained by applying, before printing, apolishing treatment with a wax solution using an organic solvent or apowder wax or a wax-like substance. Accordingly, the present inventionalso provides a solid dosage form obtained by the above-mentionedmethod, which has a print on its surface.

The solid dosage form of the present invention can be conferred adesirable characteristic of superior abrasion resistance of a printproduced on its surface, due to the presence of a coating filmcontaining polyethylene glycol on the surface of the solid dosage form.The “coating film” does not need to completely cover the surface of asolid dosage form, as long as polyethylene glycol is substantiallyuniformly present at least on the area to be printed on. For example,the “coating film” may be in the state where a number of miniature filmsattach to the surface of a solid dosage form. As used herein, by“substantially uniform” is meant being uniform to a degree sufficient toimprove the abrasion resistance of the print. Therefore, the soliddosage form of the present invention is not restricted to theabove-mentioned method, as long as it has the above-mentioned surfacestructure and superior abrasion resistance of the print, and may beproduced by any method.

Preferably, the solid dosage form of the present invention does notcontain bees wax and carnauba wax in the coating film containingpolyethylene glycol.

The solid dosage form of the present invention can be administered tothe subject in the same manner as in conventional solid dosage forms.

The present invention is explained in detail in the following byreferring to Examples, which are mere examples and do not limit thescope of the present invention in any way.

EXAMPLE 1 Reference Example Production of Film-coated Tablet Formulation(Unit: mg)

plain tablet 130.0 (containing 4 mg of active ingredient)hydroxypropylmethylcellulose 3.74 (74.8%) (TC-5; trademark) copolyvidon0.75 (15.0%) titanium oxide  0.5 (10.0%) yellow ferric oxide 0.01(0.2%)  total 135.0

Plain tablets were placed in a coating machine (Driacoater (PowrexCorporation) or Hicoater (Freund Corporation)), a film coating liquidcontaining TC-5, copolyvidon, titanium oxide and yellow ferric oxide atthe above-mentioned weight ratios was sprayed with a spray nozzle whilerotating the pan, and the tablets were dried by heated air supplied.This operation was repeated until the above-mentioned coating weight wasachieved.

EXAMPLE 2

Pre-printing Treatment with Polyethylene Glycol-containing AqueousSolution Formulation (Unit: mg) Prepar. Ex. 1 Prepar. Ex. 2 Comp. Ex.film-coated tablet 135.0 135.0 135.0 (Reference Example) MACROGOL 40000.1 (the Japan Pharmacopoeia) MACROGOL 6000 0.1 (the JapanPharmacopoeia) water (0.9) (0.9) carnauba wax 0.008 sorbitan mono-oleate0.04 n-hexane (0.9625)

The film-coated tablets (6,000 tablets, 810 g) obtained in theabove-mentioned Reference Example were placed in a Hicoater (FreundCorporation), and a 10 wt % aqueous solution of MACROGOL 4000 (the JapanPharmacopoeia; molecular weight 2,600-3,800) (Preparation Example 1) orMACROGOL 6000 (the Japan Pharmacopoeia; molecular weight 7,300-9,300)(Preparation Example 2) in total 6.0 g, or a 0.79 wt % carnauba waxn-hexane solution (Comparative Example) in total 6.063 g was sprayedwith a spray nozzle while rotating the pan to give respective tabletshaving the above-mentioned formulations.

The above-mentioned respective tablets were printed on by a conventionalmethod using an organic solvent type ink (manufactured by Colorcon.Inc.) with a tablet printing machine (Matsuoka Machinery Works Co.,Ltd).

EXAMPLE 3 Experimental Example Test of Print Abrasion Resistance of andPrinting Failure Rate

The three kinds of tablets (500 tablets each) obtained in theabove-mentioned Example 2 were visually observed to examine printingfailure, and 100 tablets each were placed in 3K glass bottles, whichwere shaken at amplitude 40 mm, shaking speed 250 times/minute in areciprocal shaker SR-IIw (Nihon Medical and Chemical instruments Co.,Ltd.) to observe the level of abrasion of the print over time. Theresults are shown in Table 1. TABLE 1 Comp. Ex. Prep. Ex. 1 Prep. Ex. 2appear- number of 500 500 500 ance test tablets Class D 0 0 0 (%)¹⁾Class C 0 0 0 (%) Class B in- 2.0 0 0 (%) complete print printing 1.41.2 0.8 stain total 3.4 1.2 0.8 abrasion 10 min print is no change (±)no change (±) property²⁾ scratchy, whole tablet is stained (+) 30 minprint is print is no change (±) scratchy, scratchy, whole whole tabletis tablet is stained (++) stained (+) 60 min print is print is print isscratchy, scratchy, scratchy, whole whole whole tablet is tablet istablet is stained (+++) stained, stained, cloudy cloudy bottle (++)bottle (++)¹⁾Class of appearanceClass B: readable print though partly missing, or printing stain of notmore than 1 mm in lengthClass C: partly unreadable print, or printing stain of more than 1 mm inlengthClass D: unreadable print²⁾Abrasion property(±): No change from the start of shaking(+): readable print though with slight change in printing state(scratching, stain and the like)(++): clear change in printing state and partly unreadable print(+++): marked change in printing state and mostly unreadable print

As is clear from Table 1, a pretreatment with a polyethyleneglycol-containing aqueous solution resulted in remarkably improvedabrasion resistance of the print as compared to the use of carnauba wax.Moreover, the printing failure rate showed a tendency toward lowerlevels. More superior results were obtained in both the abrasionresistance and printing failure rate by the use of MACROGOL 6000.

INDUSTRIAL APPLICABILITY

According to the treatment method of the present invention, printabilityand abrasion resistance of a print to be produced on a surface of thesolid dosage form can be improved, and as a result, identificationfunction of the solid dosage form can be maintained for a long time andgood appearance is not impaired, and a solid dosage form with a highcommercial value can be provided.

The method for treating a solid dosage form of the present inventionprovides an effect of remarkably improved printability and abrasionresistance of the solid dosage form by treating, before printing, thesurface of the solid dosage form with a polyethylene glycol-containingaqueous solution.

While some of the embodiments of the present invention have beendescribed in detail in the above, it is, however, possible for those ofordinary skill in the art to make various modifications and changes tothe particular embodiments shown without substantially departing fromthe teaching and advantages of the present invention. Such modificationsand changes are encompassed in the spirit and scope of the presentinvention as set forth in the appended claims.

Those described in a singular form in the present specification may beunderstood in a plural form, as long as they are not associated withclear inconsistencies with the context and the present invention.

All references cited herein, including patents and patent applications,are hereby incorporated in full by reference, to the extent that theyhave been disclosed herein.

This application is based on a patent application No. 2003-401691 filedin Japan, the contents of which are incorporated in full herein by thisreference.

1. A treatment method for improving printability or abrasion resistanceof a print to be produced on a surface of a solid dosage form, whichcomprises treating said surface with a polyethylene glycol-containingaqueous solution before printing.
 2. The method of claim 1, whereinpolyethylene glycol has an average molecular weight of not less thanabout 1,000.
 3. The method of claim 1, wherein polyethylene glycol hasan average molecular weight of about 3,000 to about 9,000.
 4. The methodof claim 1, wherein the amount of polyethylene glycol to be added by thetreatment is about 0.01% to about 1.0% in a weight ratio to the finishedpreparation.
 5. The method of claim 1, wherein the solid dosage form isa film-coated tablet.
 6. A method for producing a solid dosage form witha printed surface, which comprises treating the surface of the soliddosage form with a polyethylene glycol-containing aqueous solution andthen printing on said surface.
 7. The method of claim 6, whereinpolyethylene glycol has an average molecular weight of not less thanabout 1,000.
 8. The method of claim 6, wherein polyethylene glycol hasan average molecular weight of about 3,000 to about 9,000.
 9. The methodof claim 6, wherein the amount of polyethylene glycol to be added by thetreatment is about 0.01% to about 1.0% in a weight ratio to the finishedpreparation.
 10. The method of claim 6, wherein the solid dosage form isa film-coated tablet.
 11. A solid dosage form treated by the method ofclaim
 1. 12. A solid dosage form with a printed surface, which can beobtained by the method of claim
 6. 13. A solid dosage form which has acoating film comprising polyethylene glycol but free of bees wax andcarnauba wax on its surface, and is printed on the surface of thecoating film.
 14. A solid dosage form treated by the method of claim 2.15. A solid dosage form treated by the method of claim
 3. 16. A soliddosage form treated by the method of claim
 4. 17. A solid dosage formtreated by the method of claim
 5. 18. A solid dosage form with a printedsurface, which can be obtained by the method of claim
 7. 19. A soliddosage form with a printed surface, which can be obtained by the methodof claim
 8. 20. A solid dosage form with a printed surface, which can beobtained by the method of claim
 9. 21. A solid dosage form with aprinted surface, which can be obtained by the method of claim 10.